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Duloxetine-Induced Takotsubo Cardiomyopathy

Duloxetine-Induced Takotsubo Cardiomyopathy. Richard Perry, Pharm.D. Assistant Professor Of Pharmacy Practice Arnold & Marie Schwartz College of Pharmacy and Health Sciences Long Island University Brooklyn, New York . Takotsubo Cardiomyopathy Overview. Type of stress-induced cardiomyopathy

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Duloxetine-Induced Takotsubo Cardiomyopathy

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  1. Duloxetine-Induced Takotsubo Cardiomyopathy Richard Perry, Pharm.D. Assistant Professor Of Pharmacy Practice Arnold & Marie Schwartz College of Pharmacy and Health Sciences Long Island University Brooklyn, New York

  2. Takotsubo Cardiomyopathy Overview • Type of stress-induced cardiomyopathy • Also known as transient left ventricular apical ballooning, cardiac syndrome X and broken heart syndrome • Japanese name meaning “octopus trap” • Under recognized disease state • May mimic an acute myocardial infarction (AMI) • Found in ~1-2% of patients with suspected AMI

  3. Most commonly seen in postmenopausal women Chest pain Dyspnea ECG changes ST-segment elevation QT Prolongation ECHO findings Left ventricle: ballooning of apical and midventricular segments, hyperkinetic basal segment EF: Severely decreased Laboratory Findings CKMB, troponin, catecholamine levels Normal coronary arteries or absence of acute plaque rupture Clinical Presentation

  4. Cardiac Wall Abnormalities Scott et al. Circulation. 2005 Feb 1;111(4):472-9.

  5. Pathophysiologic Triggers • Specific cause is unknown • Possibly catecholamine mediated • Epicardial vessel spasm • Reduction in myocardial oxygen supply • Commonly preceded by acute emotional or physical stress • Vigorous excitation • Acute medical illness • Acute cocaine intoxication

  6. Duloxetine (Cymbalta®) • Serotonin and norepinephrine reuptake inhibitor (SNRI) • FDA approved for: • Major depressive disorder • Diabetic peripheral neuropathic pain (DPNP) • Generalized anxiety disorder • Initial dose for DPNP – 60 mg/daily • Metabolized through CYP450 1A2 and 2D6

  7. Case Report • 60 y/o HF (Ht, 160 cm; Wt, 58.6 kg) admitted to emergency department • CC: Chest pain, lightheadedness, nausea and diaphoresis • PMH: Type 2 diabetes mellitus, DPNP, hypertension, hypothyroidism, s/p UTI, multiple hernia and uterine fibroid surgeries • Medications on admission: Duloxetine 60 mg QAM, levothyroxine, insulin, lisinopril, aspirin, metformin, repaglinide

  8. Case Report cont`… • All: Iodine (Rash) • FH: Unknown • SH: H/O alcohol use, unemployed, living alone • PTA: Completing course of ciprofloxacin (CYP450 1A2 inhibitor) for UTI

  9. Time Course of Reaction

  10. Presentation at Hospital • Developed left sided chest pain • Nonradiating, 7/10 intensity, “pushing quality” • Diaphoretic, experiencing palpitations • Denied SOB • Vital Signs • BP, 155/105 mmHg; HR, 114 bpm; RR, 16 bpm; Temp, 98.4oF • Lungs CTA B/L

  11. Presentation at Hospital cont`… • ECG: anterior and inferolateral ST elevations, T wave inversions and prolonged QTc interval (536 msec) • Pertinent lab values on admission • Troponin I, 3.343 ng/mL; ref. range: </=0.059 ng/mL • Norepinephrine, 3492 pg/mL; ref. range: 70-750 pg/mL • C-Reactive Protein, 6.4 mg/L; ref. range: 0.215-3 mg/L Creatine kinase, 72 U/L; ref. range: 35-155 U/L

  12. Presentation at Hospital cont`… • Believed to have AMI • Given aspirin, nitroglycerin, heparin, metoprolol and clopidogrel • Rapid symptomatic improvement seen • Pt admitted to hospital • Duloxetine continued • Scheduled for cardiac catheterization and ECHO

  13. Cardiac Study Findings • Cardiac Catheterization • Normal coronary arteries • ECHO: • Akinesis of LV apex • Hyperdynamic motion of LV basal segments • EF of ~30% • Diagnosis of Takotsubo cardiomyopathy made • Heparin continued due to stasis of left ventricle, to prevent thrombus formation

  14. Hospital Time Course

  15. Patient Case Follow-Up • 39 days post-discharge • EF ~70% • LV wall segments contract normally • Slight impaired relaxation of LV • Warfarin therapy continued

  16. Discussion • Severe cardiovascular side effects uncommon with duloxetine • Possible inhibition of duloxetine metabolism by ciprofloxacin • Reaction likely due to norepinephrine surge • Temporal and causal association found between duloxetine initiation and onset of Takotsubo cardiomyopathy • Naranjo’s nomogram score 6: probable case of duloxetine-induced Takotsubo cardiomyopathy

  17. Conclusions • Takotsubo cardiomyopathy is generally transient and reversible but may mimic AMI • Clinicians must be cognizant that duloxetine may cause Takotsubo cardiomyopathy • Avoid concurrent use of CYP 450 1A2 and 2D6 inhibitors with duloxetine

  18. Thank You Questions? McCollough. Crit Care Nurse. 2007 Dec;27(6):20-7

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